PALPAIR AIAI R THERMVOPLASTYAIAI ~~~FOR BRONCHIALPALPAIR R THERMVOPLASTY INSTRUCTIONS FOR USE...

AIAI ~~~FOR BRONCHIALPALPAIR R THERMVOPLASTY

INSTRUCTIONS FOR USE

Catheter Model ATS 2-5

Only United States federal law restricts this device to sale by or on the order of a physician.

The Alair" Catheter must be used by a physician who has training and experience inperforming bronchoscopic procedures.

These Instructions for Use (IFU) are specific to the Alair® Catheter Model ATS 2-5. Do not attemptto operate the Alair® Catheter before thoroughly reading this IFU and the Alair® RadiofrequencyController Model ATS 200 Operator's Manual.

Alair® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27 ((

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Alair® System, Catheter IFU, 11678 Rev E DRAFT2010 04 09 of 27

Table of ContentsALAIR ® BRONCHIAL THERMOPLASTY SYSTEM DESCRIPTION .................... 4

IN D IC A T IO N FO R U S E ...................................................................................................... 4

BRONCHOSCOPE REQUIREMENTS ................................. 5......... .

MECHANISM OF ACTION ............................................................. 5

CONTRAINDICATIONS/ / .......................N 5

W A R N IN G S IN .................................................................. 6

PRECAUTIONSA AN... 6CLINICAL DATA........................... 8

E f ectiveN s s ..........E .......................E........................................................... . .. ........... ...........................8

M ethods .. a.... .................. .......

Statistical Plan ..... a-.... -..........................

P a tIe NI CA P o u A Tio .........................................................................................................................................................................

D be m o g r p h i s ......... ............................. ................................................ ....... _.............................................. ............................

E ff ectiven e ss Epu i tso ... ................................................................................................................ ........................ .................

E ffective ness Re u ol ts ...................... 0.............................................................................. ...................................... ................

Primary Effectiveness Endpoint - Integrated AQLO Scor................................................. 1 3

P ati t l P o lat in 1 ..................... ................................................................ ............. ..... ...................... 4

P atie nt P op u latio n .................... ...... .......................................................................... ......................... ....................... ..............

DIeCTONmographisE .... ................................................ I................. ................................. ............................ I............ ........................

Alair' Bronchial Thermoplasty System Set-up and Operation ....................................... :'..........19

E ffr C t ectieers sResut .......................................... ....................................................................................................................... 10

P osf P e ct i venes C aed p nt ..................... :................................................... ........ .......................................................... ;..................2~~~~~~~~~~~~~~~~~~~0

PrmaINTENANctieesEndon AN T O B E H TIntgrae A.LQ ......re .............. w.................... .. ... .... ........ ............................. ......................... 2

A DVERSEW A E V E N TSIN E IO TLSTY .................................................... .............. ...................................... . . ..... .............. ................. 2

W a R R A n t Y E X C Lu Saio n S ...................................................................... ...................................i .. . ........... ....................... ........ ........

L IM IT A IO N eO L A dveseLve t Y ................................. .............. .................................................... ...... ... .. .. .. ... .. ........................ .......5

S Y B O LE G E C IN D O S .......... ............ ........................... ....:.................................................I.............................I..................................2

T A E ARKS, PatheNtS, Ans pcto andPYrepartio ......................................................... ..................................................................... 127

C O N T A C T U S eparatio .................. .................. :................ - -...... ...................................... .................. ............................................... 2

Alair® Catheter Ue Usev.;.......20

Post Procedure Care ~~~~~~~~23

WARRANTYTES..................................EXCLUSIONS............................................24

DSLIEOFWARRANTY 25LSOS...............................................................................2

LIMITATION OFWARNY..... ...... LIABILITY.................i. .......................................... 26

TRADEMARKS, PATENTS, AND COPYRIGHT ................................................................27

Alair ® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

ALAIR® BRONCHIAL THERMOPLASTY SYSTEM DESCRIPTION

Figure 1: The Alair ® Bronchial Thermoplasty System

The Alair Bronchial Thermoplasty System ("Alair® System"), manufactured by Asthmatx, Inc. ("Asthmatx"), consistsof the Alair® Catheter and the Alair® Controller System, as described below:

Alair ® Catheter: The Alair ® Catheter Model ATS 2-5 ("Catheter") is provided sterile and is a SINGLE-USEONLY, disposable device. The Catheter delivers energy from the Controller to the desired site in the airway andrelays temperature feedback to the Controller. The Alair® Catheter Model ATS 2-5 is designed to be used withthe Alair® RF Controller Model ATS 200.

Alair® Controller System

Alair® Radiofrequency (RF) Controller: The Alair® RF Controller Model ATS 200 ("Controller") is designedto provide controlled delivery of RF energy to the Alair® Catheter. Energy from the Controller is delivered tothe Catheter through the electrical cable attached to the proximal end of the catheter handle. Actual powerdelivered is automatically modulated by the Controller based on temperature control algorithms. TheController delivers low-power, temperature-controlled RF energy to the airway at a predeterminedtemperature setting for a predetermined time period. The Controller incorporates hardware and softwarefeatures that limit current, voltage, power, energy, time and temperature during each application of RFenergy. The Controller is not intended to come in contact with the patient and therefore is not provided as asterile device. For information on the installation, use, and other technical specifications, please read theAlair® Radiofrequency Controller Operator's Manual that is supplied with Model ATS 200.

Footswitch: The Controller is supplied with 'a footswitch that allows the operator to start and stop thedelivery of RF energy. The Controller is designed to be used with the compatible footswitch provided byAsthmatx. The footswitch is not intended to come into contact with the patient and therefore is not providedas a sterile device.

Patient Return Electrode: The Controller is designed to be used with a gel-type patient return electrodethat is compliant with the applicable portions of IEC 60601-2-2:2006 and/or CE marked. The patient returnelectrode is used to complete the return path for the electrical current. Use only patient return electrodesindicated for use with adults or patients weighing more than 15 kg (33 lbs). Examples of acceptable patientreturn electrodes include Valleylab E7506 and ConMed 51-7310. Follow the instructions for use (IFU)packaged with the patient return electrode.

INDICATION FOR USE

The Alair® Bronchial Thermoplasty System is indicated for the treatment of severe persistent asthma in patients 18years and older Whose asthma is not well controlled with inhaled corticosteroids and long acting beta agonists.

Alair® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

BRONCHOSCOPE REQUIREMENTS

The Catheter is designed to be used with high-frequency compatible flexible bronchoscopes that have a minimum2.0mm working channel, and maximum 5.0mm outer diameter.

MECHANISM OF ACTION

Airway smooth muscle (ASM) consists of muscle tissue within the airway walls in the lung. Contraction of the ASM isa main cause of airway constriction that leads to difficulty in breathing during asthma attacks. Severe asthma patientsalso experience an increase in ASM mass. This increase, together with inflammation of the airways, combines tothicken airway walls, which decreases the inside diameter of the airways when the ASM contracts. The resultingdecrease in airway diameter causes increased resistance to airflow and further contributes to difficulty in breathingduring asthma attacks.

The Alair® System is used to deliver thermal energy to the airway wall, to heat the tissue in a controlled manner inorder to reduce ASM mass. Bronchial thermoplasty is intended to reduce, debulk, or partially eliminate smoothmuscle tissue. In preclinical studies (Danek et al. 20041, Brown et al. 20052), the reduction of ASM has been shownto decrease the ability of the airways to constrict/contract, reduce resistance to airflow and responsiveness of theairway, and increase the resting diameter of the airway.

CONTRAINDICATIONS/A/

Patients with the following conditions should not be treated:

* Presence of a pacemaker, internal defibrillator, or other implantable electronic devices,

* Known sensitivity to medications required to perform bronchoscopy, including lidocaine, atropine, andbenzodiazepines,

* Patients previously treated with the Alair® System should not be retreated in the same area(s). No clinicaldata are available studying the safety and/or effectiveness of repeat treatments.

Patients should not be treated while the following conditions are present:

* Active respiratory infection,

* Asthma exacerbation or changing dose of systemic corticosteroids for asthma (up or down) in the past 14days,

* Known coagulopathy,

* As with other bronchoscopic procedures, patients should stop taking anticoagulants, antiplatelet agents,aspirin and NSAIDS before the procedure with physician guidance.

Danek CJ, Lombard CM, Dungworth DL, Cox PG, Miller JD, Biggs MJ, Keast TM, Loomas BE, Wizeman WJ, Hogg JC, Left AR.Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs. J Appi Physiol. 2004,97(5):1946-53.

2 Brown RH, Wizeman W, Danek C, Mitzner W. Effect of bronchial thermoplasty on airway distensibility. Eur Respir J. 2005Aug;26(2):277-82.

Alair" System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

WARNINGS//l

READ THESE INSTRUCTIONS FOR USE IN CONJUCTION WITH THE ALAIR ® RF CONTROLLER MODEL ATS200 OPERATOR'S MANUAL BEFORE USING THE ALAIR® BRONCHIAL THERMOPLASTY SYSTEM. FAILURETO FOLLOW ANY INSTRUCTIONS OR FAILURE TO HEED ANY WARNINGS OR PRECAUTIONS MAY RESULTIN HARM OR INJURY TO PATIENT.

1. Prior to performing the procedure, ensure appropriate training, equipment, medications and staff are in placeto handle any potential bronchoscopic, respiratory or anesthesia related emergencies. The Alair® Systemshould only be used in a fully equipped bronchoscopy suite with access to full resuscitation equipment tohandle hemoptysis, pneumothorax, and other respiratory complications including acute exacerbation ofasthma and respiratory failure requiring intubation.

2. Do not deliver energy if the Catheter's electrode array is in contact with a metal object. This may result inharm or injury to the patient and/or operator.

3. Do not advance the Catheter within the bronchoscope if significant resistance is felt, as this may result inharm or injury to the patient and/or cause damage to the Catheter and/or bronchoscope.

4. Do not advance the Catheter into bronchi in which the Catheter cannot be seen under bronchoscopic vision.Advancing the Catheter beyond this region may cause patient harm or injury such as pneumothorax orpneumomediastinum.

5. Do not reposition the bronchoscope with the Catheter advanced beyond the distal end of the bronchoscopeas this may result in patient harm or injury.

6. Use of the Alair® Catheter with a non-Alair ® Controller may result in harm or injury to the patient and/oroperator, or may result in product malfunction.

7. Do not treat the right middle lobe because of the potential susceptibility of the right middle lobe to transientobstruction as a result of inflammation or edema due to certain anatomical characteristics. The narrowdiameter of the lobar bronchus and acute take-off angle may create poor conditions of drainage that maycause patient harrh or injury such as atelectasis or difficulty in re-inflation (Right Middle Lobe Syndrome).

PRECAUTIONS//

1 . The Alair® Catheter is provided sterile and is SINGLE USE ONLY. Do not use the Catheter if the package isopened, torn, or damaged. Use of a Catheter from damaged packaging may result in patient harm or injury.Do not re-sterilize or reuse the Catheter, as this may result in patient harm or injury, transmittal ofinfectious disease or product malfunction.

2. Do not use the Catheter if it comes in contact with a surface that is not aseptic (e.g. floor). This may result inpatient infection.

3. Do not use the Catheter if it is damaged or irregular. Use of a damaged or irregular Catheter may result inpatient harm or injury.

4. Do not use the Catheter if the marker bands are missing (See Directions for Use, Figure 5).

5. Use care when handling the Catheter to avoid kinking the Catheter shaft.

6. Avoid deflecting the bronchoscope while the electrode array is within the bend of the bronchoscope'sworking channel as this may result in damage to the Catheter and failure of the Catheter to operate properly.

7. Before inserting or removing the Catheter from the bronchoscope, ensure the electrode array is relaxed. Donot use the Catheter if the electrode array does not expand or relax properly (See Directions for Use,Figure 6 and Figure 7).

8. Before delivering energy, make certain that all electrodes are in contact with the airway wall.


9. Caution should be taken in patients with the following conditions due to a potential increased risk of adverseevents that may be associated with the procedure. Patients with these conditions were not studied in thepivotal trial and the safety of Alair® treatment for such patients has not been determined:

* Post-bronchodilator FEVy < 65% predicted.

* Other respiratory diseases including emphysema, vocal cord dysfunction, mechanical upper airwayobstruction, cystic fibrosis or uncontrolled obstructive sleep apnea.

* Use of short acting bronchodilator in excess of 12 puffs per day within 48 hours of bronchoscopy(excluding prophylactic use for exercise).

* Use of oral corticosteroids in excess of 10 milligrams per day for asthma.

* Increased risk for adverse events associated with bronchoscopy or anesthesia, such as pregnancy,insulin dependent diabetes, epilepsy or other significant co-morbidities, such as uncontrolledcoronary artery disease, acute or chronic renal failure, and uncontrolled hypertension.

* Intubation for asthma, or ICU admission for asthma within the prior 24 months.

* Any of the following within the past 12 months:

i. 4 or more lower respiratory tract infections (LRTI)ii. 3 or more hospitalizations for respiratory symptomsiii. 4 or more OCS pulses for asthma exacerbation

10. The Alair® System should only be used by clinicians who are experienced in bronchoscopy and haveundergone adequate training with the device.

11. The Alair® System should only be used in patients stable enough to undergo bronchoscopy in the judgmentof their clinician:

12. Follow local governing ordinances and your institution's biohazard procedures regarding disposal of theAlair® Catheter and patient return electrode.


CLINICAL DATA

ObjectivesThe pivotal study was a multi-center, randomized, double-blind, sham-controlled study to demonstrate the safety andeffectiveness of the Alair® System in a population of subjects with severe asthma.

Effectiveness EndpointsThe primary effectiveness endpoint was the difference between treatment (Alair) and control (Sham) groups in thechange in the Asthma Quality of Life Questionnaire (AQLQ) score between baseline and the average of 6-, 9-, and12-month follow-up visits (integrated AQLQ score). Other endpoints included: rates of severe asthma exacerbations,proportions of patients with severe asthma exacerbations, and days lost from work, school, or other daily activitiesdue to asthma symptoms. In addition, several safety endpoints were considered for effectiveness; these endpointsincluded rates of asthma (multiple symptoms)* adverse events, Unscheduled Physician Office visits for respiratorysymptoms, Emergency Room visits for respiratory symptoms, and Hospitalizations for respiratory symptoms.

"Asthma (multiple symptoms)" is defined as occurrence or worsening of shortness of breath, wheeze, cough, productive cough, orsome combination of these.

MethodsThis was a multicenter, randomized (2 Alair, 1 Sham), double-blind, sham-controlled clinical trial comparing theeffects of treatment with the Alairo System to a Sham treatment in subjects that were optimized to conventionaltherapy of inhaled corticosteroids (ICS) and long-acting j32-agonists (LABA). All subjects included in the Study weretaking ICS (> 1000pg beclomethasone or equivalent per day) and LABA (_> 100pg salmeterol or equivalent per day),and were still symptomatic.

Subjects in the Alair and Sham groups were administered the Alair® treatment and Sham bronchoscopies;respectively, by an unblinded bronchoscopy team in 3 separate bronchoscopy sessions. Each bronchoscopy sessionwas separated by at least 3 weeks. All bronchoscopy sessions were administered under local anesthesia withsedation. Subjects had follow-up visits with blinded asthma assessment teams at 6-weeks, 12-weeks, 6-months, 9-months, and 12-months after the final bronchoscopy session.

All subjects were prescribed to take 50mg of oral prednisone or prednisolone (or equivalent) each day for 5 dayscovering the 3 days before the bronchoscopy session, the day of the bronchoscopy session, and the day after thebronchoscopy session (prophylactic indication).

Statistical PlanPrimary and secondary endpoints, as well as adverse events were analyzed using Bayesian statistics. The PosteriorProbability of Superiority was calculated for the primary and secondary endpoints, as well as safety outcomes,

Patient PopulationEnrollment was limited to patients with severe persistent asthma who were still symptomatic despite being managedon conventional therapy of high dose ICS and LABA. Subjects may have been taking up to 10 milligrams of oralcorticosteroids per day. Study subjects were required to meet the following patient selection criteria:

Key Entry Criteria

Inclusion

1. Adult; age 18-65 years.2. Asthma requiring regular maintenance medication that includes inhaled corticosteroids (greater than 1OOOpg

beclomethasone per day or equivalent) and long-acting 32-agonists (at least 100pg salmeterol per day or

Alair® System, Catheter IFU, 11678 Rev E DRAFT.2010 04 09 of 27

equivalent), with or without other asthma medications. Oral corticosteroids at a dosage of up to, but notgreater than 10mg per day, or 20 milligrams every other day are acceptable.

3. Asthma Quality of Life Questionnaire Score during the Baseline Phase of 6.25 or less.4. Pre-bronchodilator forced expiratory volume in one second >60% predicted (after patients stabilized on

inhaled corticosteroids and long-acting j32-agonists during the Baseline Phase).5. Non-smoker x 1 year or greater (if former smoker, less than 10 pack years total smoking history).

Exclusion

1. Post-bronchodilator FEVy <65% predicted.2. Three or more hospitalizations for exacerbations of asthma in the previous year; OR a history of life-

threatening asthma, defined by past intubations for asthma, or intensive care unit admission for asthmawithin the prior 24 months.

3. History of recurrent lower respiratory tract infection requiring antibiotics (more than 3 in the past 12-Months).4. History of recurrent oral steroid use for asthma (4 or more pulses of oral steroids in the past 12-Months).

DemographicsA total of 297 subjects between the ages of 18 and 65 were enrolled and randomized (2 Alair: 1 Sham) in this study.One hundred and ninety (190) received the Alair® treatment and 98 received the Sham control treatment (Intent-to-Treat population). The Sham procedure was identical to the Alair ® procedure except that no energy was deliveredthrough the Catheter.

There were no statistical differences in demographic measures between the Alair and Sham groups. Subjectdemographics are described in Table 1.

Alair Sham(n=190) (n=98)

Age (years) (Mean + SD) 41 ± 12 41 ± 12

Gender

Male 81 (43%) 38 (39%)

Female 109 (57%) 60 (61%)

Race/Ethnicity

Caucasian 151 (80%) 72 (74%)

African American / Black 19 (10%) 15 (15%)

Hispanic 6 (3%) 4 (4%)

Asian 4 (2%) 1 (1%)

Other 10 (5%) 6 (6%)

Height (cm) (Mean ± SD) 167 ± 9 167 + 10

Weight (kg) (Mean ± SD) 82 ± 18 82 ± 20

Table 1: Subject Demographics (Intent-to-Treat Population)

Alair® System, Catheter IFU, 11678 Rev E DRAFT 20100409 of 27

Effectiveness ResultsEffectiveness analyses were performed for both the Intent-to-Treat (ITT) population and Per-Protocol (PP) population.The ITT population consisted of all randomized subjects who have been administered at least one bronchoscopy.The PP population excluded all subjects in the ITT population who met any of the following criteria:

• Have taken any interfering concomitant medications.

* Have undergone other interfering treatments.

* Did not attend one of the 6-, 9-, 12-month visits, with the exception of a discontinuation from the Studydue to an adverse event related to Study treatment.

* Had missed one or more bronchoscopy procedures.

Effectiveness Endpoints

Although the clinical study was powered only for the primary effectiveness endpoint (see below), severaleffectiveness endpoints and safety endpoints that could also be considered effectiveness endpoints demonstratedclinically meaningful differences in favor of the Alair group compared to the Sham group. The effectiveness endpointswere rates of severe asthma exacerbations, proportions of patients with severe asthma exacerbations, and days lostfrom work, school, or other daily activities due to asthma symptoms. The safety endpoints considered foreffectiveness were rates of asthma, emergency room visits for respiratory symptoms, and hospitalization rates forrespiratory symptoms.

Steroid Exacerbations a (Severe Exacerbations Requiring Systemic Corticosteroids) (ITT Population)

During the Post-Treatment Phase, the severe exacerbation rate for the Steroid Exacerbations was 0.48exacerbations/subject/year in the Alair group and 0.70 exacerbations/subject/year in the Sham group [95% CI (Sham- Alair): -0.031, 0.520]. During the Post-Treatment Phase, the proportion of subjects experiencing SteroidExacerbations was 26% in the Alair group and 40% in the Sham group [95% Cl (Sham - Alair): 2.1%, 25.1%].

Steroid Exacerbation rates (annualized rate) and proportion of patients experiencing Severe Exacerbations for thePost-Treatment Phase are presented graphically in Figure 2.


Severe Exacerbation Rates (Steroid),45 - Proportion of Subjects

1.0

c 400.9 .o.

39.8

·0.8 35U

u 0.7 xE 0.70

0.6 25

0 0.520

w 0.415 -5U

Cu 0.3 1152 10>i 0.2

· i 50.1 I.

0.0 ,Sham Alair Sham Alair

Figure 2: Severe Exacerbations during the Post-Treatment Phase

"Steroid Exacerbations = Exacerbations treated with oral or intravenous corticosteroids, OR a doubling of thebaseline inhaled corticosteroid dose for at least 3 days, OR any temporary increase in the dosage of oralcorticosteroids for a subject taking maintenance oral corticosteroids at Study entry.

Annualized rates of exacerbations per subject are extrapolated from the 46 week Post-Treatment Phase from 6weeks after the last bronchoscopy procedure to the 12 month follow-up visit.

Alair ® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

Days Lost from Work, School, or Other Daily Activities due to Asthma Symptoms (ITT Population)

During the Post-Treatment Phase, subjects in the Alair group lost an average of 1.3 days/year/subject from work,school, or other daily activities due to asthma symptoms, compared to the Sham group that lost 3.9 days/year/subject(annualized rates per subject are extrapolated from the 46 week Post-Treatment Phase from 6 weeks after the lastbronchoscopy procedure to the 12 month follow-up visit) [95% Cl (Sham - Alair): 0.425, 6.397].

Safety Endpoints that Demonstrated Effectiveness

Measures such as Emergency Room visits and Hospitalizations for respiratory symptoms are generally considered tobe important measures of safety, especially if an intervention results in an increase in the rate of one or more of theseevents. However, these measures can also be considered important measures of effectiveness if an interventionresults in a measurable decrease in the rate of one or more of these events. During longer-term follow-up (> 6 weeksafter the last Alair ® treatment), there was a reduction in asthma (multiple symptoms) adverse events [95% Cl (Sham -Alair): -0.01, 0.001], Emergency Room visits for respiratory symptoms [95% Cl (Sham - Alair): 0,11, 0.83], andHospitalizations for respiratory symptoms (event rate per group) [95% Cl (Sham - Alair): 0.025, 0.172, presentedgraphically in Figure 3.

There was a reduction in the proportion of subjects having asthma (multiple symptoms) adverse events ([95% Cl(Sham - Alair): 4.0%, 27.3%]), and in the proportion of subjects having Emergency Room visits for respiratorysymptoms in the Alair group (3.7% in the Alair group compared to 15.3% in the Sham group) [95% Cl (Sham - Alair):4.6%, 19.7%].

SISAlair® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

Safety Endpoints Demonstrating Effectiveness

0.8

0.7 -0 Sham

~. 0.6>(D 0.6 - 9~~~~~~~~~~~~~~~~~[ Alair

j 0.5 0

0.201- 0.2

0 2-di

0.1

Asthma (Multiple Unscheduled Emergency Room HospitalizationsSymptoms) Physician Office Visits

Visits

Figure 3: Safety Endpoints demonstrating Effectiveness (ITT Population)

Primary Effectiveness Endpoint- Integrated AQLQ Score

The difference between the Alair and Sham groups in the average change in AQLQ score from Baseline at the 6-, 9-,and 12-month follow-up visits was 0.210 [95% CI (Alair - Sham): -0.025, 0.445]. The pre-specified PosteriorProbability of Superiority for the difference between the groups was 96.4%. For the ITT population, the differencebetween the groups had a Posterior Probability of Superiority of 96.0%, and for the PP population, the differencebetween the groups had a Posterior Probability of Superiority of 97.9%, demonstrating an improvement in the AsthmaQuality of Life in the Alair group compared to Sham.

The results for the change from Baseline of the Integrated AQLQ score for the Intent-to-Treat and Per Protocolpopulations are summarized in Table 2.

Difference Between Groups in PosteriorPopulation Integrated AQLQ Score Probability of

(Posterior Mean, 95% Cl) Superiority (%)

ITT (Intent-to-Treat) 0.210(Alair N=190, Sham N=98) ('0.025, 0.445)

PP (Per Protocol) 0.244 97.9(Alair N=173, Sham N=95) (0.009, 0.478)

Table 2: Primary Effectiveness Endpoint: Integrated AQLQ Score

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ADVERSE EVENTS IN PIVOTAL STUDY

Patient PopulationThe Alair® System was evaluated in a randomized, double-blind, sham-controlled, multi-center clinical study - theAsthma Intervention Research 2 (AIR2) Trial. A total of 297 subjects with severe persistent asthma who were stillsymptomatic despite being managed on conventional therapy of high dose ICS and LABA were randomized - 196subjects in the Alair group and 101 subjects in the Sham group. (See the Clinical Data section for key entry criteria.)The Sham procedure was identical to the Alair® procedure except that no energy was delivered to the Catheter in thesham procedure.

Safety analyses were performed for the Intent-to-Treat (ITT) population (288 subjects) that consisted of allrandomized subjects who have been administered at least one bronchoscopy.

Observed Adverse EventsThe safety of the Alair® System was assessed by comparing adverse event profiles of the Alair and Sham groupsubjects. Adverse event profiles are compared for the Treatment Phase (day of first bronchoscopy procedure to 6weeks after the last bronchoscopy procedure) and Post-Treatment Phase (6 weeks after the last bronchoscopy to the12 month follow-up visit).

Adverse events (whether considered procedure-related or not procedure-related by the investigator) occurring with >3% incidence that were more common in the Alair group are presented for 288 patients in Table 3.

S


Treatment 3 Post-treatment4

Alair Sham Alair ShamAdverse Event (N=190) (N98) (N187) (N=98)

Average duration of period (days) 84 322Ear, Nose, and Throat

Upper respiratory tract infection 20 11 30 26Viral Upper respiratory tract infection 4 2 6 7Nasopharyngitis 5 7 11 5Acute Sinusitis 3 2 4 8Rhinitis 2 0 4 6

Lower Respiratory

Asthma (Multiple Symptoms) 52 39 27 43Wheezing 15 6 4 3Dyspnea 11 6 2 1Bronchitis 4 2 7 5Chest discomfort 9 10 2 1Atelectasis 5 0 0 0Hemoptysis 3 0 0 0Lower respiratory tract infection 8 2 3 6Chest pain 14 13 3 1

Neurology

Anxiety 4 0 1 2Headaches 14 9 5 3

Gastrointestinal

Dyspepsia 4 2 2 4Nausea 3 4 1 1

Non-site specific

Pyrexia (fever) 4 2 0 1Influenza 4 2 4 12

Other

Urinary tract infection 1 1 3 1Hypertension 3 2 3 3

Table 3: Adverse Events with > 3% Incidence (% of subjects) that were more common in the Alair Group

3 Treatment phase represents adverse events reported between the first bronchoscopy and 6-weeks post last bronchoscopy.

4 Post-Treatment phase represents adverse events reported between 6-weeks post last bronchoscopy and the 12 month visit.


Adverse events occurring in both the Treatment Phase and Post-Treatment Phase at a rate of <3% and ->1%(whether considered procedure-related or not procedure-related by -the investigator) that were morefrequently reported by the Alair group than the Sham group included pneumonia, operative hemorrhage,abnormal breath sounds, bronchial obstruction, acute bronchitis, bronchospasm, lower respiratory tractinfection (viral), pulmonary congestion, discolored sputum (blood-tinged sputum), increased upper airwaysecretion, and viral pharyngitis.

During the Treatment Phase in the AIR2 Trial, there was a transient increase in respiratory adverse events, includingasthma (multiple symptoms), upper respiratory tract infection, atelectasis, lower respiratory tract infection, wheezing,hemoptysis, and anxiety in the Alair group compared to the Sham group. There was a lower incidence of throatirritation in the Alair group compared to the Sham group. There were 7 instances of hemoptysis defined as >5.0 mL(1.3% of bronchoscopies) of which 2 occurred on the day of the procedure, 2 occurred within 3 days, ·2 occurred at 2weeks, and one occurred on Day 31 after the procedure. The greatest amount of hemoptysis observed was acumulative total of 150 mL that occurred over 5 days and was treated with bronchial artery embolization.

During the Treatment Phase (- 12 weeks period), the rate of Unscheduled Physician Office visits (events / subject /12 weeks) in the Alair group was 0.230 compared to 0.133 in the Sham group. The rate of hospitalizations forrespiratory symptoms (events / subject / 12 weeks) was 0.086 in the Alair group compared to 0.028 in the Shamgroup. The rate of Emergency Room visits for respiratory symptoms (events / subject / 12 weeks) was 0.062 in theAlair group compared to 0.075 in the Sham group.

During the Post-Treatment Phase in the AIR2 Trial, there was a lower incidence of respiratory symptoms in the Alairgroup compared to the Sham group, including a 36% reduction in asthma (multiple symptoms) events and proportionof subjects with asthma (multiple symptoms) events. There was also a lower incidence of influenza, and a greaterincidence of nasopharyngitis in the Alair group compared to the Sham group.

High Resolution Computed Tomography (HRCT) Results

In the 150 subjects (100 Alair group and 50 Sham group) assigned to HRCT scan examinations, at 1-year, there wereno difference in signs of gas trapping or consolidation and there was no evidence of bronchiectasis. A difference wasseen in bronchial wall thickening without gas trapping which occurred only in the Sham subjects (4%).

Summary of Clinical Findings

Results from the clinical study which evaluated the effectiveness and safety of the Alair® System in subjects withsevere asthma demonstrated that Alair® treatment resulted in clinically significant reductions in severe exacerbationsthat required systemic steroids, the percent of subjects experiencing the severe exacerbations, the number ofEmergency Room visits for respiratory symptoms, the percent of subjects experiencing Emergency Room visits forrespiratory symptoms, Hospitalizations for respiratory symptoms, and days lost from school/work/other daily activitiesdue to asthma symptoms. Although bronchial thermoplasty was associated with an increased rate of respiratoryadverse events during the Treatment Phase (primarily related to asthma), in the Post-Treatment Phase, a smallerproportion of patients treated with bronchial thermoplasty experienced respiratory adverse events, including asthma(multiple symptoms).


DIRECTIONS FOR USE

Alairt Catheter Inspection and Preparation

1. The Alair® System should only be used by a physician trained in bronchoscopy. These instructions do notexplain bronchoscopic procedures.

2. Please read the Operator's Manual for the Alair® RF Controller Model ATS 200 before beginning theprocedure.

3. Visually inspect the package for damage before removing the Catheter from the package. Do not use theCatheter if the package is damaged or has been previously opened or torn.

4. Aseptically remove the Catheter from the package tray and inspect for any damage. The Catheter ispackaged with the electrode array retracted within the protective, removable orange-colored Catheter tipsheath. Before use, remove the protective orange sheath. Inspect the Catheter for any damage such asbroken or crushed areas of the Catheter, sharp or protruding edges at the distal tip, or any excessive bendsor kinks in the Catheter shaft. Do not use the Catheter if any damage or irregularity is found. See Figure 4.

0

Figure 4: Alair® Catheter in Tray

5. The distal portion of the Catheter shaft has marker bands that are spaced 5mm apart to aid in thepositioning of the Catheter electrode array. Do not use the Catheter if the marker bands are missing. SeeFigure 5.

Figure 5: Alair® Catheter with its four Marker Bands, spaced 5mm apart


6. Hold the Catheter handle in the palm of your hand, with the thumb and forefinger just below the Alair® logo.Then, squeeze the forward handle back towards the back handle, ensuring that the electrode array expandsproperly. Verify that the electrode array opens fully and evenly. See Figure 6.

Figure 6: Alair® Catheter Electrode Array Expanded

7. Relax the electrode array by releasing the front handle. See Figure 7. Do not use the Catheter if theelectrode array does not expand or relax properly.

Figure 7: Alair® Catheter Electrode Array Relaxed

Alairo System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

Figure 8: Alair ® RF Controller Set-up

Alair Bronchial Thermoplasty System Set-up and Operation

The Alair® Catheter is intended to be used in conjunction with the Alair ® Controller. Please read the Alair® REController Model ATS 200 Operator's Manual before using the Alair System.

Figure 8 illustrates the Alair' RF Controller Model ATS 200 set up.

Consult the Alair ® RF Controller Model ATS 200 Operator's Manual for specific instructions on:

* Controller Installation;

* Controller Power-Up;

- Connection of Components and Accessories;

- Controller Modes;

* Periodic Maintenance and Repair;

* T roubleshooting; and

* Technical Specifications.

Alair® System, Catheter I FU, 11678 Rev E DRAFT 2010 04 09 of 27

Patient Preparation

1. Administer prophylactic prednisone or equivalent at a dosage of 50 mg/day for the 3 days before theprocedure, the day of the procedure and the day after the procedure to minimize post procedure inflammation.

2. Verify the patient remains a good candidate for bronchoscopy under moderate sedation prior to initiation of theprocedure (Mayse et al 2007) 5. Postpone the procedure if any of the following conditions apply:

* Prescribed prednisone was not taken on the 3 days before bronchoscopy.

* SpO 2 is less than 90% on room air.

* Increase in asthma symptoms in last 48 hours requiring more than 4 puffs/day on average of rescuebronchodilator over pretreatment usage.

· Asthma exacerbation or changing dose of systemic corticosteroids for asthma (up or down) in the past14 days.

* Active respiratory infection, active allergic sinusitis, or other clinical instability.

* Physician feels for any reason the procedure should be postponed.

3. Prepare the patient for bronchoscopy. Follow patient management protocols according to staffing, training,and individual institution-specific policies and guidelines for bronchoscopy.

4. * Place the patient return electrode securely on the patient in accordance with manufacturer's instructions.

5. Introduce the flexible bronchoscope through the nose or mouth as appropriate. See Figure 9 below.

Figure 9: Bronchoscope navigation into patient's airways

6. Navigate the bronchoscope to the targeted site and position the bronchoscope so that the targeted site is inbronchoscopic view.

Alair®Catheter Use

1. Before inserting the catheter into the bronchoscope, ensure the electrode array is relaxed.

2. Advance the catheter into the bronchoscope working channel being careful not to kink the catheter shaft.Kinking of the catheter shaft could result in failure of the catheter electrode array to open fully in tortuousanatomy. See PRECAUTIONS.

S Mayse ML, Laviolette M, Rubin AS, Lampron N, Simoff M, Duhamel D, Musani, Al, Yung RC, Mehta AC. Clinical Pearls forBronchial Thermoplasty. J Bronchol. 2007, 14:115-123.

Alair ®System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

3. Avoid deflecting the bronchoscope while the electrode array is within the bend of the bronchoscope'sworking channel as this could result in damage to the Catheter and failure of the Catheter to operateproperly. See PRECAUTIONS.

4. Advance the Catheter through the bronchoscope until the distal tip of the Catheter shaft is in bronchoscopicview. If the device encounters significant resistance during insertion, do not force it. In especially tortuousanatomy it may be necessary to relax the bronchoscope's deflection mechanism until the device passessmoothly. See Figure 10 below.

Figure 10: Alair® Catheter introduced through working channel of bronchoscope

5. Advance the Catheter to the targeted site under bronchoscopic vision. Do not advance the Catheter intobronchi in which the Catheter cannot be seen under bronchoscopic vision. Advancing the catheter undersuch conditions may result in pneumothorax, pneumomediastinum or other harm or injury to the patient.See WARNINGS.

6. Do not treat the right middle lobe because of the potential susceptibility of the right middle lobe to transientobstruction as a result of inflammation or edema due to certain anatomical characteristics. The narrowdiameter of the lobar bronchus and acute take-off angle may create poor conditions of drainage that maycause patient harm or injury such as atelectasis or'difficulty in re-inflation (Right Middle Lobe Syndrome).See WARNINGS.

7. Do not reposition the bronchoscope with the Catheter advanced beyond the distal end of the bronchoscopeas this may result in harm or injury to the patient. See WARNINGS.

8. Once at the targeted site, squeeze the handle together to expand the electrode array partially so that theelectrodes are close to or just touching the targeted site.

9. With the electrode array partially expanded, adjust the axial position of the electrodes in the airway toposition the active electrodes (exposed 5mm center region of the array electrodes) as desired. Expand thearray until all four electrodes firmly contact the airway wall. Do not over-expand the electrode array as thismay cause one or more of electrodes to deploy inward or 'invert'. If an electrode inverts, relax the electrodearray and then re-expand the array in a large, straight airway, confirming proper deployment before returningto the area being treated. In most cases, full expansion of the Catheter electrode array will NOT require thecatheter handle to be squeezed completely.

10. Proper contact of the electrodes with the airway wall should be confirmed visually. See Figure 11 below.


Bronchoscope

Elctrode Array

Figure 11: Alair® Catheter in the Airway

11. Before delivering RF energy, make certain that all electrodes are in contact with the airway wall. SeePRECAUTIONS.

12. Deliver RF energy to the targeted region by pressing and releasing the footswitch once. The Controller willdeliver energy automatically according to preset parameters for time, energy, power, and temperature.

13. To manually terminate RF energy delivery, if necessary, press and release the footswitch again.Note: The Controller will automatically shut off the RF energy if it detects atypical energy delivery ortemperature response.

14. The Controller is programmed to alert the user with both audible and visual cues if re-deployment of theelectrode array or replacement of the Catheter is required. Please refer to the Alair® RF Controller ModelATS 200 Operators Manual for more detailed instructions on these audible sounds and light displays.

Note: If RF energy delivery ends prematurely, it may be necessary to re-deploy the electrode array and beginRF energy delivery again. If the problem persists, replace the Catheter

15. Reposition the Catheter and repeat the steps above making 5mm proximally placed contiguous treatments.The catheters marker bands are spaced 5mm apart to assist with contiguous placement. See Figure 12.

Catheter plaid Electrode ary Elecrode amy Electode any Electodearmydistally in airway, partially cllaped e· nded and parially collpad anded andele6od army and moed 5 n adjae not and nwvd adjacenbt notcpanded and p:odrrnl top ,,M otvedapping. Act it- poioral to pieioun ove.lep.ing. ctiva-

controller aivated activation tion =mnpleted acditmltn tion cormplted

Figure 12: Contiguous Placement and Activation


16. Once the procedure is complete, relax the Catheter handle to relax the electrode array before removing theCatheter from the bronchoscope or before withdrawing the Catheter into the bronchoscope for airwaynavigation. To manipulate the bronchoscope with the Catheter in the working channel, withdraw theCatheter approximately 10 cm into the bronchoscope so the electrode array is proximal to the bend in thedistal tip of the bronchoscope.

17. Once the treatment is complete, remove the Catheter from the bronchoscope. Disconnect the Catheter fromthe Controller, and dispose of the used Catheter per your institution's biohazard procedures. Remove thereturn electrode from the patient. Disconnect the patient return electrode from the Controller, and dispose ofthe patient return electrode per your institution's biohazard procedures.

Post Procedure Care

1. Follow appropriate institutional guidelines for post procedure care. It is recommended that patients shouldbe carefully monitored and discharged only after they are deemed to be stable and have adequate(comparable to pre-procedure) lung function, mental status, and are able to adequately take liquids.

2. Recommended post procedure assessments are based on the criteria that were used in clinical trials ofbronchial thermoplasty (Mayse et al 2007) and include:

* 2 to 4 hour recovery/monitoring period followihng each procedure

* Spirometry, breath sounds, and vital signs (heart rate, blood pressure, temperature, respiratory rate,pulse oximetry) before discharge

* Discharge if post bronchodilator FEVy is within 80% of the pre procedure value and patient is feelingwell

* Verify patient has gag reflex and is able to take liquids

* Remind patient to take prophylactic prednisone or equivalent the day following bronchoscopy

* Caution patient about the potential adverse events that they might experience including hemoptysis,fever, cough, and worsening of asthma symptoms. Patients should be advised to consult their physicianif they experience any of these adverse events, or asthma symptoms that are not controlled by theirreliever medications.

* Contact patient via phone calls at 1, 2 and 7 days to assess post procedure status

* Office visit at 2 to 3 weeks to assess clinical stability and schedule subsequent bronchial thermoplastyprocedures as appropriate

A Sy ,t r 16 R D F 0 4P 2o

Alair~ System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

HOW SUPPLIED

The Alair® Bronchial Thermoplasty System Catheter Model ATS 2-5 is supplied sterile and is for SINGLE USE ONLY.Do not re-sterilize or reuse the Catheter, as this may result in patient harm or injury, transmittal of infectiousdisease, or product malfunction.

MAINTENANCE AND TROUBLESHOOTING

* If mucus builds up in the airways and obscures visualization, remove the catheter from the bronchoscope,provide irrigation with sterile saline, and suction the resulting fluid from the airways.

* If the electrode array does not expand or relax properly, remove the Catheter from the bronchoscope andsqueeze and relax the Catheter handle to visually confirm that the electrode array is functioning properly. If it isnot functioning properly, replace the Catheter and continue with the bronchial thermoplasty procedure.

I If you are alerted to auditory or visual cues from the Controller, consult the Alair® Bronchial Thermoplasty RFController Model ATS 200 Operator's Manual for operating and troubleshooting guidelines for the Controller.

CUSTOMER SERVICE

All questions or concerns related to the Catheter should be directed to Asthmatx Customer Service or an authorizedAsthmatx representative. No product may be returned without prior authorization. Please contact AsthmatxCustomer Service or an authorized Asthmatx representative for a Return Material Authorization (RMA) number. See"Contact Us".

PRODUCT WARRANTIES

Asthmatx warrants until the expiration date marked on each Product (the "Warranty Period"), the Alair® Catheter soldhereunder will be free from material defects in materials, function and workmanship and will conform to Asthmatx'sspecifications in effect as of the date of manufacture. This limited warranty extends only to Customer as originalpurchaser unless otherwise agreed upon in writing by Asthmatx.

If during the Warranty Period: (i) Asthmatx is notified promptly upon discovery of any defect in the Alair® Catheter (ii)such Alair® Catheter is returned, shipping charges prepaid, to Asthmatx's designated facility with the prior approval ofAsthmatx with a valid RMA number, and (iii) Asthmatx's inspections and tests determine that the Alair ® Catheter isindeed defective and the Alair® Catheter has not been subjected to any of the conditions set forth below under"Warranty Exclusions," then, as Customer's sole remedy and Asthmatx's sole obligation under the foregoingwarranty, Asthmatx will, at Asthmatx's option, replace without charge the defective Alair® Catheter or provideexchange credit. Any Alair® Catheter that has been replaced under this warranty shall have warranty coverage untilthe expiration date marked on the replacement Alair Catheter.

WARRANTY EXCLUSIONS

THE WARRANTY SET FORTH IN "PRODUCT WARRANTIES" SHALL NOT APPLY IF THE DEFECTIVE ALAIR®CATHETER (A) HAS BEEN SUBJECTED TO ABUSE, MISUSE, NEGLECT, NEGLIGENCE, ACCIDENT,IMPROPER TESTING, IMPROPER INSTALLATION, IMPROPER STORAGE, IMPROPER HANDLING OR USECONTRARY TO ANY DOCUMENTATION OR INSTRUCTIONS ISSUED BY ASTHMATX, (B) HAS BEENREPAIRED OR ALTERED, (C) HAS NOT BEEN INSTALLED, OPERATED, AND MAINTAINED IN ACCORDANCEWITH THE DOCUMENTATION OR OPERATED OUTSIDE OF THE ENVIRONMENTAL SPECIFICATIONS FORTHE ALAIR® CATHETER; (D) HAS FAILED DUE TO AN ACT OF NATURE, INCLUDING BUT NOT LIMITED TOFIRE, FLOOD, TORNADO, EARTHQUAKE, HURRICANE OR LIGHTNING OR (E) HAS BEEN USED WITH ANY

/

Alair® System, CatheterlIFU, 11678 Rev EDRAFT 2O1004O09 of27

DEVICES, ACCESSORIES OR EQUIPMENT NOT MANUFACTURED BY OR APPROVED BY ASTHMATX FORTHE ALAIR® SYSTEM. IN ADDITION, THE FOREGOING WARRANTY SHALL NOT APPLY TO ALAIR®CATHETER(S) (A) MARKED OR IDENTIFIED AS "EVALUATION," OR "DEMONSTRATION" OR "NOT FORHUMAN USE" OR (B) LOANED OR PROVIDED TO CUSTOMER AT NO COST.

DISCLAIMER OF WARRANTY

EXCEPT FOR THE WARRANTIES SET FORTH IN "PRODUCT WARRANTIES", ASTHMATX MAKES NO OTHERWARRANTIES, EXPRESS, IMPLIED OR STATUTORY, WITH RESPECT TO ANY ALAIR® CATHETER(S) OROTHER PRODUCTS PROVIDED IN CONNECTION WITH YOUR CATHETER AGREEMENT, INCLUDINGWITHOUT LIMITATION ANY IMPLIED WARRANTY OF MERCHANTABILITY, IMPLIED WARRANY OF FITNESSFOR A PARTICULAR PURPOSE, WARRANTY OF NONINFRINGEMENT, OR ANY IMPLIED WARRANTYARISING FROM COURSE OF PERFORMANCE, DEALING, USAGE OR TRADE.

LIMITATION OF LIABILITY

IN NO EVENT SHALL ASTHMATX OR ITS SUPPLIERS BE LIABLE TO CUSTOMER OR ANY THIRD PARTYFOR COSTS OF PROCUREMENT OF SUBSTITUTE ALAIR® CATHETERS OR SERVICES, LOST PROFITS,DATA OR BUSINESS, ALAIR® CATHETER RE-USE, ALAIR® CATHETER USE BY NON-QUALIFIED PHYSICIANALAIR® CATHETER USE CONTRARY TO DOCUMENTATION, ALAIR® CATHETER USE WITH A NON-ALAIR®CONTROLLER, DAMAGES ARISING FROM BREACH BY THE CUSTOMER, INCLUDING WITHOUT LIMITATIONANY INTENTIONAL, WILLFUL, OR NEGLIGENT ACTS OR OMISSIONS BY CUSTOMER OR ITS EMPLOYEESOR AGENTS WITH RESPECT TO PATIENTS, OR FOR ANY INDIRECT, SPECIAL, INCIDENTAL, EXEMPLARYOR CONSEQUENTIAL DAMAGES OF ANY KIND ARISING OUT OF OR IN CONNECTION WITH YOURCATHETER AGREEMENT OR WHICH MAY RESULT FROM THE USE OF ALAIR® CATHETER(S) PURCHASEDHEREUNDER, HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY (WHETHER IN CONTRACT, TORT(INCLUDING NEGLIGENCE), STRICT LIABILITY, PRODUCTS LIABILITY OR OTHERWISE). ASTHMATX'STOTAL, CUMULATIVE, AND EXCLUSIVE LIABILITY ARISING OUT OF OR IN CONNECTION WITH ANY ALAIR®CATHETERS PURCHASED BY CUSTOMER HEREUNDER SHALL IN NO EVENT EXCEED THE PURCHASEPRICE PAID BY CUSTOMER FOR SUCH ALAIR® CATHETER. THE LIMITATIONS SET FORTH IN THISSECTION SHALL APPLY EVEN IF ASTHMATX OR ITS SUPPLIERS HAVE BEEN ADVISED OF THEPOSSIBILITY OF SUCH DAMAGES, AND NOTWITHSTANDING ANY FAILURE OF ESSENTIAL PURPOSE OFANY LIMITED REMEDY.

A[air® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

SYMBOL LEGEND

7RE F] Model Number

Caution: Consult Accompanying Documents

VTFJ ILCR Radiation sterilized. Sterility guaranteed ifpackage unopened or undamaged.

L OT Lot Number

Manufacturer Name

Use by

For SINGLE-USE ONLY.

For sale or use by or on order of a physician

XxOnly only


TRADEMARKS, PATENTS, AND COPYRIGHT

AsthmatxGAlair®, /IAk and Asthmatx are registered trademarks of Asthmatx, Inc. Other product names mentioned in theseInstructions For Use may be the trademarks or the registered trademarks of their respective companies and arehereby acknowledged.

US Patent Nos. 7,556,624; 7,425,212; 7,273,055; 7,264,002; 7,200,445; 7,198,635; 7,104,987; 7,027,869; 6,634,363;6,488,673; and 6,411,852; and Patents Pending. The purchase of the Alair® Catheter does not grant a license, eitherexpressly, by implication, estoppel or otherwise under any Asthmatx patent right or patent (including without [imitationU.S. Patent Nos. 7,556,624; 7,273,055; 7,264,002; 7,027,869; 6,634,363; 6,488,673; or 6,411,852) covering orrelating to any method or process in which the Alair ® Catheter might be used. An implied license only exists for theAlair Catheter used in conjunction with Asthmatx's Alair® ATS 200 Controller. Nothin% herein shall be construed asa right or license to (a) make, use, sell, offer to sell, import, lease or distribute Alair Catheters with a non-AlairoController or (b) sell or offer to sell Alair® Catheters to customers that plan to make, have made, use, sell, offer to sell,import, lease or distribute Alair ® Catheters with a non-Alair® Controller. Asthmatx may have patents or pending patentapplications, trademarks, copyrights or other intellectual property rights covering subject matter in this IFU. Thefurnishing of this IFU does not give you any license to these patents, trademarks, copyrights or other intellectualproperty rights except as expressly provided in any written license agreement from Asthmatx.

Information in this IFU may change periodically. Please read this IFU and the Alair® RF Controller Operators Manualregularly. No part of this IFU may be reproduced or transmitted in any form or by any means, electronic ormechanical: for any purpose, without the express written permission of Asthmatx.

Copyright © 2009 Asthmatx, Inc. All rights reserved.

CONTACT US

Manufacturer:Asthmatx, Inc.888 Ross Drive, Suite 100Sunnyvale, CA, 94089 USAPhone: 408-419-0100Fax: 408-419-0199Email: customerservice(asthmatx.comwww.asthmaix.com

G0Alair® System, Catheter IFU, 11678 Rev E DRAFT 2010 04 09 of 27

Patient Brochure

Alair ®Bronchial Thermoplasty System

CoverThis brochure describes a new procedure for treating severe asthma in adults.

Page 1 of 12

Contents

Why doctors use this .......................................................................................................... 3

What is the ALAIR SYSTEM? .3

What is BT? ................................................. 3

Who can have this treatment? (Indication for Use) ........................................................... 4

Who cannot have this treatment? (Contraindications) ...................................................... 4

What are the Risks and Side Effects of BT? ........................................................................ 6

What are the Benefits of BT? ...................... a...................... 8

What will happen if you decide to have the BT treatment for your severe asthma? ........ 8

After each BT treatment. ................................................................................................. 11

Where to learn more about the ALAIR SYSTEM and BT: .................................................. 11

About Severe Asthma ...................................... ................................................................ 11

Page 2 of12 12

Why doctors use thisYou have severe asthma. Your asthma is severe because the asthma drugs you takenow do not control your asthma symptoms.

Your doctor wants to use the ALAIR SYSTEM to treat your severe asthma. This treatmentis called Bronchial Thermoplasty (BT). BT is not an asthma medicine. Yo ur doctor thinksyour health is good enough to have this done.

If you decide to have this treatment, you will need to do what your doctor asks you todo or you may be harmed.

What is the ALAIR SYSTEM?The ALAIR SYSTEM has two main parts:

* A small tube with 4 wires at the end. See Figure 1.

Figure 1: Actual size of tip of ALAIR tube

* A machine that heats the wires.

You need to decide if BT is right for you. You will be treated by a doctor who has beentrained and knows how to use it correctly.

What is BT?BT shrinks the muscles in your airway walls by heating them. This may allow yourairways to stay more open and helIp you breathe better.

Page 3 of 12 7

Who can have this treatment? (indication for Use)The Alair Bronchial Thermoplasty System is indicated for the treatment of severepersistent asthma in patients 18 years and older whose asthma is not well controlledwith inhaled corticosteroids and long acting beta agonists.

Who cannot have this treatment? (Contraindications)You cannot have this treatment if you, have:

* An implant with electronics. Tell your doctor if you have any implants. BT maykeep the implant from working correctly.

* Problems taking certain drugs. Tell your doctor if you have ever had a problemtaking any kind of drugs. Your doctor will use some drugs to perform BT. Yourdoctor needs to make sure the drug he or she uses will not hurt you.

* Have had this treatment before. Tell your doctor if you have had BT before.

* You cannot have this treatment if you are less than 18 years old. No one hastested BT in patients younger than 18 years.

You cannot have this treatment while the following conditions are present:* An active respiratory infection. Tell your doctor if you think you have an

infection, fever, or your asthma is worse than usual. If your infection is in yourlungs or airway, BT may harm you.

* Have had an asthma attack or changed your oral corticosteroid dose in the last2 weeks. Tell your doctor if either of these happened in the last 2 weeks. If youhave had an asthma attack or changed your oral corticosteroid dose in the last 2weeks, BT may harm you.

* A blood clotting problem. Tell your doctor if you take any drugs to keep yourblood from clotting. Some call these drugs blood thinners. if you have a bloodclotting problem, BT may harm you.

Clinical StudyIn 2007, doctors studied nearly 300 patients who had severe asthma. In this study, theysaw how well BT worked and what side effects patients had. Doctors treated about 200people with BT. This was the "BT Group". Doctors treated another group in a similarway, but they did not heat their airways. This was the "Sham Group". Patients did notknow which group they were in. Doctors studied these patients for a year after their

Page 4 of 12 7

last treatment. We do not know how well patients did beyond one year. This is stillI ~~being studied.

Page 5 of 12 93

What are the Risks and Side Effects of BT?Right after their doctors treated them, many patients in the study had side effects.Table 1 shows how many people had each side effect. The table shows side effects thatoccurred in 1 or more out of every 100 patients, and occurred more often in the BTgroup.

Table 1: Short Term and Long Term Side Effects

Short-Term Period Long-Term Period

Type of Side Effect BT Group ISham Group BTGop FSham Group

Related to Breathing (out of every 100 patients) (out of every 100 patients)

More than one symptom of asthma 52 39 27 43

Wheezing is 6 4 3

Chest pain 14 13 3 1

Shortness of breath 1 1 6 2I

Chest discomfort 9 10 2 1

Infection in the lower airways s 2 3 6

Collapse of part of the lung a 0 0

Swelling of the airways 4 2 7 5

Bleeding 3 0 0 0Blocked airways 3 0 0 0

Pneumonia 2 0 3 2

Blood in mucus 2 1 1 1

Abnormal breath sounds 2 0 0 0

Intense swelling of airways 1 1 0 0 0Infection in the lower airways caused by a virus 1 0 0 0

Narrowing of airways 1 0 0 0

Fluid in Fungs 1 0 0 0

Related to Ear, Nose and Throat

Infection in the upper airways 20 11 30 26

Swelling of the nose and/or throat 5 7 11 5Infection in the upper airways caused by a virus 4 2 6 7

Acute Sinusitis 3 2 4 8

Rhinitis 2 0 4 6

Swelling of throat 2 1 1 1

Increased mucus in upper ai rways 1 0 0 0

All other

Headaches 14 9 5 3

Fever 4 2 0 1

Influenza 4 2 4 12

Upset stomach 4 2 2 4

Anxiety 1 4 1 0 1 2

Page 6 of 12 (

Short-Term Period Long-Term Period

Type of Side Effect BT Group Sham Group BT Group Sham Group

Nausea 3 411

High blood pressure 3 21 3 3

Urinary tract infection 1 1 3 1

Bleeding dluring the procedure 1 0 0 0

One instance of bleeding occurred 31 days after a BT treatment and was treated with a medical procedure.

How to read this table:* Short term: from start of first treatment until 6 weeks after third treatment.* Long term: from 6 weeks after last treatment until 1 year after last treatment.* In the table, some patients had more than one side effect.* Look at Table 1.

o Think of a group of 100 patients.o Look at the column that says "short term'.o Go down that column to the row that reads "more than one symptom of

asthma."o This row means that 52 out of every 100 patients had "more than one

symptom of asthma" sometime after their first treatment until 6 weeksafter their third treatment.

o On the same row, now look at the "long term" column.o You see there were 27 out of every 100 patients who had "more than one

symptom of asthma" in the long term period.o The 52 and the 27 are not separate groups of patients. Some patients

may be counted in both groups:* One or more patients who had a "short term" effect may have

also had a "long term" effect. Meaning he or she did not getbetter.

* One or more patients who did not have a "short term" effect mayhave had a "long term" effect. Meaning he or she got worse lat er.

* One or more patients who had a "short term" effect may not havehad a "long term" effect. Meaning their problem went away.

o We do not know how well patients will do beyond ayear after theirtreatment.

Page 7 of 12

What are the Benefits of BT?

The study showed that the people in the BT Group had fewer severe asthma attacks,visits to the emergency room, and asthma symptoms as shown in Figure 2.

Figure 2: Benefits of BT

Decrease in Decrease in Decrease in100 - Severe Asthma Emergency Asthma

; 90 Attacks Room Visits Symptoms

' 80C0

, 700

60 60

40

30 3

20

I0

10

U Sham Group * BT Group

The BT Group also lost on average 3 fewer days per patient from work, school, or otherdaily activities due to asthma symptoms. This was for one year after treatmentcompared to the Sham Group. This is not shown in Figure 2.

What will happen if youdecide to have the BT treatment foryour severe asthma?

* There will be 3 treatments. There will be 3 weeks in between each treatment.* You will prepare for each treatment by taking a 50-mg steroid pill by mouth once

a day for 3 days before the treatment.· You will also take a 50-mg steroid pill on the day of the treatment.* On each BT treatment day, your doctor will test your lungs. He or she will do this

by checking how much air you can blow out.* Your doctor will make sure you don't have an infection. An infection would delay

the treatment.

Page 8 of 12

· Your doctor will tell you what he or she will do during BT.* Your doctor will:

1. Give you drugs to make you sleepy.2. Put a small tube called a bronchoscope through your mouth into your

airways. See Figure 3.

Figure 3: Placement of Bronchoscope into your lungs

Bronchoscope placed throughthe mouth into the lung

3. Put the smaller ALAIR tube through the bronchoscope. The wires on its endwill touch your airways. See Figure 4.

Figure 4: Placement of ALAIR tube in your lungs

Wires of ALAIR tube opened tocontact the inside of your airways

Page 9 of 12

4. Heat the wires on the end of the small ALAIR tube to reduce some of theairway muscle tissue. You won't feel this because your doctor gave you drugs.See Figure 5 for how airways look before and after.

Figure 5: Airways Before and After BT Treatment

Airway of Person Without Asthma

Normal band of AirwayMuscle

Open Airway where air travels

Airway of Person with Severe Asthma

More Airway Muscle causesairway to narrow

This is the area where Alair appliesheat to the airway wall during BTtreatment

Airway of Person with Severe Asthma after Treatment

Reduced Airway Muscle afterBT Treatment

After BT, the inside airway wall andother tissue heals, BUT AirwayMuscle is reduced

5. Move the small ALAIR tube to more places and treat them the same way.6. Take the small ALAIR tube and the bronchoscope out.7. Watch over you as you wake up and recover.

Page 10 of 12

After each BT treatment,* You have to take 50-mg steroid pill the day after.* Your doctor will contact you by phone to check on you:

o the day after your treatmento the day after that, ando a week after your treatment

* You wil still have to take your asthma medicine.

After your airways heal from your first treatment, you will go back to your doctor foryour second treatment. Your doctor will treat more of your airways. After you get wellfrom that, your doctor will treat the rest of your airways in your third treatment.

Use your rescue inhaler if your asthma symptoms get bad. Tell your doctor if youneeded to use your rescue inhaler.

Where to learn more about the ALAIR SYSTEM and BT:- Contact your doctor, or

* Call:

Asthmatx, Inc.888 Ross Drive, Suite 100Sunnyvale, CA 94089www.asthmatx.com

Toll Free: 877-810-6060

About Severe AsthmaWhat happens when you have severe asthma?Air travels in and out of your lungs through airways, which are tubes. There are tinymuscles in the walls of the airways. People who have severe asthma have larger musclesin their airways than other people. The airways close down when these muscles contract.

Page 11 of 12

What happens when your airways close down?When airways close down it can be harder to breathe. Your chest may feel tight. Youmay wheeze or cough. Asthma medicines usually open up the airways. Thesemedicines do not always work well in patients who have severe asthma.

Thank you for considering this new treatment for severe asthma.

Alair, Asthmatx, Asthmatx Mark, and bronchial thermoplasty mark are registeredtrademarks of Asthmatx, Inc.

10-003 Rev. A Date of Printing: DD MON YYYY

(Asthmatx Patient Brochure_13APR2010_FINAL)

Page 12 of 12 s:oC

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